This is an application for a K23 award for Dr. Beth Cohen, a general internist at the University of California, San Francisco who is conducting patient-oriented research to reduce cardiovascular disease (CVD) in patients with post-traumatic stress disorder (PTSD). PTSD is an increasingly common illness that causes substantial mental and physical disability. Patients with PTSD are at greatly increased risk for developing CVD, but the underlying mechanisms are not known. Dr. Cohen's goal is to determine how PTSD increases CVD risk and to translate these findings into interventions that will reduce CVD morbidity and mortality in the growing number of veterans and civilians living with PTSD. To accomplish this, Dr. Cohen will analyze 3 populations that vary by length of exposure to PTSD and stage of CVD. Using a database of over 200,000 veterans returning from Iraq and Afghanistan, Dr. Cohen will compare levels of established CVD risk factors and rates of incident CVD in those with and without PTSD (Aim 1). Dr. Cohen will also conduct a pilot prospective cohort study to examine established and novel CVD risk factors in a group of older veterans and civilians without known CVD (Aim 2). Finally, using an ongoing prospective cohort, she will conduct an ancillary study of 820 men and women with known CVD to determine which biological, behavioral, and psychosocial mechanisms link PTSD to recurrent CVD events (Aim 3). This research will provide preliminary data for an R01 to conduct a larger prospective cohort study to identify targets for future intervention studies. To accomplish these research goals, Dr. Cohen will pursue training in: (1) adapting administrative and healthcare data for patient-oriented research, (2) advanced longitudinal data analysis, (3) the design and conduct of prospective cohort studies, and (4) psychosocial and cardiovascular disease measures. Dr. Cohen has assembled an outstanding multidisciplinary mentorship team, comprised of a primary mentor Dr. Mary Whooley, an expert CVD epidemiology, Dr. Charles Marmar, a psychiatrist who is an expert in PTSD epidemiology and treatment, and Dr. Eric Vittinghoff, an expert in study design and biostatistical analysis. In addition, Dr. Cohen has advisors from cardiology (Dr. Nelson Schiller), internal medicine (Dr. Karen Seal), and the social sciences (Dr. Judith Moskowitz). This dedicated mentorship team, combined with a rigorous, supportive research environment, will ensure Dr. Cohen develops into a successful independent investigator.